1. Field of the Invention
This invention is in the field of recombinant DNA technology and relates to ribozymes.
2. Description of the Related Art
The art is currently exploring the many different ways of attacking the human immunodeficiency viruses (HIV), represented by HIV-1 and HIV-2 or the cellular mechanisms involved in infection by HIV and its progress in vivo. It has recently been shown that (HIV) and simian immunodeficiency virus (SIV) enter target cells by forming a complex between the viral envelope protein and two cell-surface membrane receptors: CD4 and a transmembrane chemokine receptor. Isolates of HIV that differ in cellular tropism use different subsets of chemokine receptors as entry cofactors: macrophage-tropic HIVs primarily use CCR5, whereas dual-tropic isolates use both CCR5 and CXCR4 (also called “Fusin”) receptors; CXCR4 is also used by T-tropic viruses.
The role of CCR5 has been reviewed by S. O'Brien and M. Dean, Scientific American, 28-35 (September 1997). That review suggests several ways in which this stage of the HIV infection or maintenance might be blocked. These include:                obstructing the binding site on CCR5 for HIV by use of chemokine derivative which competes with the natural chemokines or by use of synthetic antibodies,        vaccination with fragments of CCR5,        new genes whose products would prevent CCR5 from being made or would stop CCR5 from serving as a docking site for HIV.        
PCT Application Publication No. WO 97/45543 proposes to inhibit the action or production of CCR5 receptors in a variety of ways including therapy with antibodies; making variants of CCR5 to use as decoys, thus interfering with the fusion of cells; by way of agents which bind to CCR5 and antisense oligomers and ribozymes to prevent expression of the DNA coding for CCR5.
PCT Application Publication No. WO 97/44055 similarly proposes many ways of inhibiting the action or production of CCR5 receptors, broadening the concept to extend to other chemokine receptors including CXCR4.
In Antiviral Agents Bulletin 10 (No. 9), 261-262 (September 1997), an article “Trojan Horse Virus' Controls HIV in vitro”, it is reported that vesicular stomatitis virus (VSV) modified to express CD4 and CXCR4 can selectively target and kill HIV cells in vitro. This approach is described as problematical but “does highlight the potential to use HIV-mimicking attenuated viruses or liposomes with surface cellular HIV receptors for targeted delivery of HIV protease inhibitors, other antiretroviral drugs, antisense agents, gene therapies, ribozymes or other agents to HIV-infected cells.”